AGED Triad of Vascular Aging Linked to Biomarkers of Alzheimer Disease

The AGED triad (apathy, gait disturbances, and executive dysfunction), a vascular aging phenotype associated with mood, mobility, and cognitive impairment, has been linked to biomarkers of Alzheimer disease (AD) according to a study presented at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference. The multicohort cluster analysis also affirmed the phenotype’s relevance across ethnic groups. Awareness of the AGED triad could help clinicians identify high-risk patients early, leading to improved clinical intervention, particularly for diverse populations.

Researchers examined systolic and diastolic blood pressure (BP), apathy, gait speed (GS), and executive function (EF) data from 2 samples of older adults enrolled in the Daily Activity Study of Health (DASH; n=37) and the Healthy Aging Brain Study (HABS; n=52). The researchers also examined the distribution of AD biomarkers across the HABS cohort, including total tau, plasma phosphorylated tau181 (p-tau181), amyloid beta (Aβ) 40 and 42, and the Aβ42/40 ratio. Three distinct groups were identified in both the DASH and HABS cohorts, with data about AD biomarkers coming exclusively from the HABS cohort:

• Cluster 1 had normal BP, no apathy, fast GS, the highest EF scores, and no reported AD biomarkers.  
• Cluster 2 had high BP, significant apathy, slow GS, the lowest EF scores, and elevated levels of total tau and p-tau181. 
• Cluster 3 had normal BP, apathy, slow GS, moderate EF scores, and higher Aβ42/40 ratios.

The difference in EF scores was statistically significant (P<.05) between healthy individuals (Cluster 1) and those exhibiting the AGED phenotype (Cluster 2). The results also suggest a strong association between vascular aging and AD biomarkers (Cluster 2) and a potential non-vascular contribution to the AGED phenotype (Cluster 3). 

These patterns were externally validated in the HABS: Health Disparities (HABS-HD) cohort, which is comprised of 758 African American, 1196 Mexican American, and 1196 non-Hispanic White participants, suggesting the AGED triad’s relevance to a diverse population.